Health-related quality of life in patients with KRAS-mutated chemorefractory metastatic colorectal cancer treated with sotorasib plus panitumumab or standard of care (CodeBreaK 300): results from a phase 3, randomised clinical trial.

Background: In the phase 3 CodeBreaK 300 study, sotorasib (KRAS inhibitor) plus panitumumab (EGFR inhibitor) significantly prolonged progression-free survival versus investigator's choice of trifluridine-tipiracil or regorafenib (standard of care) in patients with KRAS-mutated chemorefractory metastatic colorectal cancer. This analysis evaluated patient-reported outcomes (PROs) as secondary and exploratory endpoints.

Methods: In this open-label, randomised clinical trial, adult (aged ≥18 years) patients from 67 centres in 13 countries in Asia, Australia, Europe, and North America with KRAS-mutated chemorefractory metastatic colorectal cancer (as assessed by central molecular testing of tumour biopsy specimens) who were KRAS inhibitor-naive, had progressed to recurrence after previous therapy with fluoropyrimidine, oxaliplatin, and irinotecan, with measurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.

Impact of perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel delivery on postoperative survival in locally advanced oesophagogastric adenocarcinoma.

Background: Perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is the standard of care for locally advanced oesophagogastric adenocarcinoma (LA-OGA) in Western countries. However, completing treatment is challenging for patients, particularly in the postoperative setting. This study investigated the impact of adjuvant chemotherapy (ACT) administration and treatment completion on survival outcomes in patients receiving FLOT.

Does Gait Assistance Modulate Reflex Excitability in Those with Spasticity? A Preliminary Study.

Stiff-Knee gait (SKG) is a common post-stroke impairment, marked by insufficient knee flexion during the swing phase, which reduces toe clearance, increases fall risk, and requires compensatory movements that can have adverse biomechanical effects. To address muscle weakness and paresis in SKG, assistive technologies, such as functional electrical stimulation (FES) and robotic exoskeletons, have been introduced. However, robotic assistance may inadvertently increase spinal reflex excitability by activating muscle stretch receptors, potentially worsening SKG.

Case studies in neuroscience: movement-related cortical stimulation to enhance corticospinal transmission in chronic incomplete spinal cord injury.

Incomplete spinal cord injury (iSCI) disrupts signal transmission at the level of injury (LOI) and in higher brain structures, weakening intracortical circuits and impairing movement initiation. A potential approach to target intracortical circuits is to deliver transcranial magnetic stimulation (TMS) during motor intention, known as movement-related cortical stimulation (MRCS). We hypothesize that delivering TMS during motor intention will enhance corticospinal excitability (CE) and improve muscle activation below the LOI.

Single-room transcatheter CT hepatic angiography for microwave liver ablation: a feasibility and safety study.

Objectives: Transcatheter CT hepatic angiography (CTHA) enhances liver tumour ablation by enabling multiple direct intra-arterial contrast injections during a single procedure. We report the implementation of a single-room CTHA workflow using a mobile fluoroscopic C-arm, focusing on feasibility and safety.

Methods: A prospective service evaluation was conducted following a radiation risk assessment and training at an expert centre.

Ablative Techniques for Lung Metastases: Patient Selection and Outcomes Following Treatment with Stereotactic Radiotherapy or Radiofrequency Ablation.

Stereotactic radiotherapy (SBRT) and radiofrequency ablation (RFA) are common ablative techniques for lung metastases. A retrospective review of all patients treated with either modality at a single institution between 2011 and 2019 was conducted. Baseline characteristics and outcomes were compared.

Characteristics of Ipsilateral Corticomotor Pathways in People with cervical spinal cord Injury.

Objective: Understanding motor neurophysiology is important for developing effective upper limb treatments for people with tetraplegia following cervical spinal cord injury (SCI). While literature has primarily focused on contralateral motor pathways, neurophysiology of ipsilateral pathways remains largely unexplored in tetraplegia. We aimed to investigate ipsilateral physiology and its relationship to upper limb function in individuals with tetraplegia.

Human Cortico-Cerebellar Dynamics During Motor Error Processing After Stroke.

The cerebellum acts as a forward internal model to predict motor outcomes, compare them with sensory feedback, and generate prediction errors that refine prediction accuracy. Our physiological understanding of cerebellar function during motor control derives predominantly from animal experiments and clinical observations in patients with disorders of the cerebellum or its connections with the cerebrum and spinal cord. Here, we report a human electrophysiology-based investigation of cerebello-thalamo-cortical pathway activity during motor error detection and correction.

Maintenance Capecitabine Plus Ramucirumab After First-Line Chemotherapy in Patients With Advanced Esophagogastric Adenocarcinoma: Results From the Randomized PLATFORM Study.

Purpose: PLATFORM is an adaptive phase II study assessing maintenance therapies in advanced esophagogastric adenocarcinoma (OGA). We evaluated the role of capecitabine plus a vascular endothelial growth factor receptor 2 inhibitor ramucirumab (cape-ram) in these patients.

Methods: Human epidermal growth factor receptor 2 (HER2)-negative patients with advanced OGA with stable or responding disease after 18 weeks of induction platinum-based chemotherapy were randomly assigned 1:1 to surveillance or cape-ram.

Early rituximab monotherapy versus watchful waiting for advanced stage, asymptomatic, low tumour burden follicular lymphoma: long-term results of a randomised, phase 3 trial.

Background: Initial results of this study, reported after a median follow-up close to 4 years, demonstrated improved time to initiation of new treatment (TTNT) for patients with advanced stage, asymptomatic, low tumour burden follicular lymphoma who received early rituximab monotherapy when compared with watchful waiting. Given the long natural history of follicular lymphoma, the trial was extended to further assess TTNT with longer follow-up. Mature data are presented here.

Stratification algorithm for repetitive TMS in stroke (START): Results from an exploratory crossover study.

The role of contralesional motor cortices in paretic upper extremity (UE) motor recovery following stroke varies based on available structural reserve. However, an optimal measure of the reserve to stratify patients for different contralesional brain stimulation remains unknown. This study aimed to establish severity criteria distinguishing which patients benefit more from inhibitory contralesional motor cortex (M1) stimulation versus facilitatory contralesional dorsal premotor cortex (cPMd) stimulation.

Real-world evidence to support health technology assessment and payer decision making: is it now or never?

Objectives: The aim of this policy article is twofold: (i) to provide a summary and update of recent important policy developments, in particular relevant guidance on the use of real-world data/real-world evidence (RWD/RWE) by health technology assessment (HTA) bodies and (ii) to set out our policy recommendations on how the different elements of an "RWE framework" we have previously developed could support, further enhance and facilitate the use of RWE for HTA purposes and by HTA bodies and payers.

Methods: We undertook a targeted review and analysis of recent important policy developments. The aim was to build on our recommendations from previous work on the "RWE Framework," and consider how the relevant tools from our Framework can further enhance and facilitate the use of RWE for HTA purposes and by HTA bodies/payers.

Disease-free survival as surrogate for overall survival in esophageal cancer: An individual patient data meta-analysis of neoadjuvant chemotherapy and chemoradiotherapy.

Background: The use of surrogate endpoints may expedite the reporting of study outcomes of clinical trials. The validity of disease-free survival (DFS) as a surrogate for overall survival (OS) in the neoadjuvant treatment of esophageal (E) or gastroesophageal junctional (GEJ) carcinomas remains uncertain.

Objective: To evaluate DFS as a surrogate end-point for OS in E/GEJ using the meta-analytical approach DESIGN, SETTING, AND PARTICIPANTS: individual patient data from an international meta-analysis on operable locally advanced E/GEJ, which including randomized trials comparing at least two of the neo-adjuvant treatment strategies: upfront surgery (S), chemotherapy followed by surgery (CS), and/or chemoradiotherapy followed by surgery (CRS).

Intra-patient comparison of microarchitecture of tumour negative lymph nodes from oesophageal cancer patients - Results from the MRC Oe02 trial.

Background: Regional lymph node (LN) status is a key prognostic factor in oesophageal cancer (OeC). Tumour-derived antigens can activate immune reactions in LNs, potentially reflecting the host's anti-tumour immune response. It remains unclear whether this response is homogeneous across all tumour negative LNs (LNneg) within individual OeC patients.

Mechanisms of Post-stroke Stiff-Knee Gait: A Narrative Review.

Stiff-Knee gait is a dysfunction commonly observed post-stroke characterized by a decreased swing phase knee flexion angle. Importantly, Stiff-Knee gait can impair walking, ultimately reducing overall activity and participation. Interventions for Stiff-Knee gait have shown mixed results and, combined with more recent observational evidence, suggest that there are other potential causes requiring the need to re-examine its etiology.

Evaluation of objective methods for analyzing ipsilateral motor evoked potentials in stroke survivors with chronic upper extremity motor impairment.

Ipsilateral motor evoked potentials (iMEPs) are believed to represent cortically evoked excitability of uncrossed brainstem-mediated pathways. In the event of extensive injury to (crossed) corticospinal pathways, which can occur following a stroke, uncrossed ipsilateral pathways may serve as an alternate resource to support the recovery of the paretic limb. However, iMEPs, even in neurally intact people, can be small, infrequent, and noisy, so discerning them in stroke survivors is very challenging.

Pancreatic Adenocarcinoma: Long-Term Outcomes of Adjuvant Therapy in the ESPAC4 Phase III Trial.

Purpose: The ESPAC4 trial showed that adjuvant chemotherapy with gemcitabine plus capecitabine (GemCap) produced longer overall survival (OS) than gemcitabine monotherapy. Subsequently, the PRODIGE24-CCTG PA.6 trial showed even longer survival for modified fluorouracil, folinic acid, irinotecan, and oxaliplatin (mFOLFIRINOX) than gemcitabine but had more restrictive eligibility criteria.

Quality of life in advanced-stage, asymptomatic, non-bulky follicular lymphoma treated with rituximab shows significant improvement compared with watchful-waiting.

Traditionally, patients with asymptomatic, advanced-stage follicular lymphoma were managed with a watchful-waiting approach until disease progression. The 'Watch and Wait' Phase-3 randomised international trial examined whether rituximab could delay the need for treatment and the effect on quality of life (QoL). In this article, we present the long-term results of the QoL aspect of the trial.

Incidental finding of leukaemia in circulating tumour DNA- the importance of a molecular tumour board.

As the use of liquid biopsies are increasing across multiple indications in cancer medicine, the detection of incidental findings on circulating tumour DNA is of increasing importance. We report the finding of leukaemia detected in a patient who underwent plasma-based circulating tumour DNA next generation screening as part of a screening liquid biopsy study. A BRAF V600E mutation detected was deemed pathogenic following discussion at a molecular tumour board, and recommendation of further investigations led to the diagnosis of an occult haematological malignancy.

Surgical Outcomes Following Neoadjuvant Treatment for Locally Advanced and Borderline Resectable Pancreatic Ductal Adenocarcinoma.

Objective: To assess overall survival (OS), compare the effects of neoadjuvant treatment, and describe surgical outcomes for patients undergoing pancreatic resection following chemotherapy and/or chemoradiotherapy (CRT) for borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC).

Background: We approach BR/LA PDAC using chemotherapy followed by selective CRT to the primary site of disease where either the surgical margin remains radiologically threatened following chemotherapy or as a further downstaging treatment.

Methods: Retrospective study of patients between December 2005 and June 2023 at the Royal Marsden Hospital, London, United Kingdom.